Myocardial perfusion imaging with single photon emission tomography (SPECT) remains critically important for diagnosing and assessing coronary artery disease (CAD). The ability to differentiate normal myocardial regions from those that are ischemic or infarcted is essential for patient management and for determining patient prognosis. Currently, cardiac SPECT imaging requires at least two imaging sessions to obtain perfusion images under stress and under rest conditions, with each imaging session lasting 15 to 20 min. Furthermore, second generation SPECT/CT imagers now are available that can combine myocardial perfusion imaging with anatomical assessment of the heart with computed tomography; SPECT/CT therefore has the potential to provide a complete perfusion study combined with CT assessment of cardiac mechanics (ejection fraction, stroke volume, myocardial thickening), coronary patency, and status of coronary calcification in a single dual-modality imaging session. However, a combined SPECT/CT myocardial protocol would take up to 60 min, with virtually all of this time needed for SPECT, and would make poor utilization of this expen- sive equipment in the clinic and therefore may be cost prohibitive. Therefore, in this study the investigators propose to develop multipinhole SPECT imaging techniques with the goal of improving detection efficiency by 20-fold while maintaining or improving the spatial resolution in comparison to current SPECT imaging techniques. In addition, the investigators hypothesize that this method will allow simultaneous dual isotope imaging due to an improved signal to noise ratio of the multipinhole approach, which represents a further reduction in study time. The study encompasses the following specific aims: (1) We will develop and build a 20-pinhole collimator imaging system optimized for clinical myocardial perfusion imaging. (2) We will perform experiments to determine the minimal number of views of a multipinhole collimator sufficient to minimize angular sampling artifacts of the heart. We will obtain myocardial perfusion images of an anthropomorphic phantom with SPECT that are correlated with high-resolution anatomical images with CT and we will implement methods of correcting the SPECT image for attenuation using a priori structural information. (3) We will evaluate simultaneous dual-isotope imaging of myocardial perfusion with a multipinhole collimator. In this study, we will demonstrate that cross-talk correction of simultaneous 201TI/99mTc imaging can be improved significantly in the projection data acquired with a multipinhole collimator versus that obtained with a parallel hole collimator. Overall, successful development of multipinhole SPECT/CT promises to substantially increase the feasibility and cost-effectiveness of a comprehensive assessment of myocardial status and cardiac function in a way that will promote improved care and management of patients with coronary artery disease. ' [unreadable] [unreadable] [unreadable]